A single-arm, two-stage, open-label, phase 2 study investigating the safety and efficacy of intravesical gemcitabine/docetaxel for bacillus Calmette-Guerin (BCG)-naïve patients with non-muscle invasive bladder cancer (NMIBC). All participants will receive an induction course of gemcitabine/docetaxel instillations followed by maintenance instillations if initial efficacy is seen. In addition to providing initial efficacy data, this study will provide safety and long-term efficacy data on the combination regimen studied. A tolerable safety profile and demonstrated efficacy would support a potential, randomized phase 3 trial comparing the experimental combination therapy and standard of care intravesical BCG therapy.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||July 29, 2020||Phase 2||Interventional|
Primary Outcome 1 - Measure: 3-Month Complete Response Rate
Primary Outcome 1 - Time Frame: 3 months
1. Histologically confirmed intermediate or high-risk non-muscle invasive urothelial
carcinoma of the bladder (Ta, T1, or Tis stage) on TURBT obtained within 90 days of
registration defined according to modified EORTC risk criteria summarized as follows:
1. Low-risk tumors: Initial or recurrent tumor > 12 months after resection with all
of the following:
- Solitary tumor
- < 3 cm
- No carcinoma in situ (CIS)
2. Intermediate-risk tumors: All tumors not defined in the two adjacent categories
(between the category of low- and high-risk)
3. High-risk tumors: Any of the following:
- T1 tumor
- Multiple and recurrent and large (> 3 cm) Ta low-grade tumors (all
conditions must be met for this point of Ta low-grade tumors)
4. Note #1: Low-risk tumors as defined above are not eligible
5. Note #2: Mixed histologies are permitted, provided a component of urothelial
carcinoma is present
6. Note #3: All patients with high-grade T1 (HGT1) should undergo a restaging TURBT
2. Eastern Cooperative Oncology Group (ECOG) (WHO) performance status 0, 1, or 2
3. Age ≥ 18 years old at time of consent
4. Evidence of post-menopausal status or negative urinary or serum pregnancy test or
female pre-menopausal patients is required. Women will be considered post-menopausal
if they have been amenorrheic for 12 months without an alternative medical cause. The
following age-specific requirements apply:
1. Women <50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy).
2. Women ≥50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses >1 year ago, had
chemotherapy-induced menopause with last menses >1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
5. Subjects who give a written informed consent obtained according to local guidelines.
1. Subjects with muscle-invasive (i.e. T2, T3, T4), locally advanced unresectable, or
metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained
within 90 days prior to study registration. The required radiographic imaging
1. Abdomen/Pelvis - CT scan
2. Chest - chest x-ray or CT scan
2. Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) urothelial
carcinoma of any stage.
a. Note: Subjects with history of non-invasive (Ta, Tis) upper tract urothelial
carcinoma that has been definitively treated with at least one post-treatment disease
assessment (i.e. cytology, biopsy, imaging) that demonstrates no evidence of residual
disease are eligible.
3. Subjects with another active second malignancy with an estimated overall survival from
the second malignancy of < 12 months. Subjects with another second active malignancy
that are deemed to have an estimated overall survival of >12 months are eligible.
4. Subjects who have received the last administration of an anti-cancer therapy including
chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting
study drug, or who have not recovered from the side effects of such therapy.
5. Subjects who have had radiotherapy ≤ 4 weeks prior to starting study drug, or who have
not recovered from radiotherapy toxicities.
6. Pregnant or breast-feeding women.
7. Subjects unwilling or unable to comply with the protocol.
8. Patients with prior systemic gemcitabine or docetaxel use for a non-bladder malignancy
may enroll and receive treatment.
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Max Kates, MD
Role: Principal Investigator
Affiliation: Johns Hopkins University
Name: Max Kates, MD
|Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland 21287
Max Kates, MD